Search results for "deficiency"

Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning.

2021

Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2′-o-ribose methyltransferase). Supported by…

Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection.

2021

Although antiretroviral therapy suppresses HIV replication, it does not eliminate viral reservoirs or restore damaged lymphoid tissue, posing obstacles to HIV eradication. Using the SIV model of AIDS, we investigated the effect of mesenchymal stem/stromal cell (MSC) infusions on gut mucosal recovery, antiviral immunity, and viral suppression and determined associated molecular/metabolic signatures. MSC administration to SIV-infected macaques resulted in viral reduction and heightened virus-specific responses. Marked clearance of SIV-positive cells from gut mucosal effector sites was correlated with robust regeneration of germinal centers, restoration of follicular B cells and T follicular h…

Combined B, T and NK Cell Deficiency Accelerates Atherosclerosis in BALB/c Mice.

2016

This study focused on the unique properties of both the Ldlr knockout defect (closely mimicking the human situation) and the BALB/c (C) inbred mouse strain (Th-2 slanted immune response). We generated two immunodeficient strains with severe combined B- and T-cell immunodeficiency with or without a complete lack of natural killer cells to revisit the role of adaptive immune responses on atherogenesis. C-Ldlr-/- Rag1-/- mice, which show severe combined B- and T-cell immunodeficiency and C-Ldlr-/- Rag1-/- Il2rg-/- mice, which combine the T- and B-cell defect with a complete lack of natural killer cells and inactivation of multiple cytokine signalling pathways were fed an atherogenic Western ty…

Peritransplant Antiviral Treatment of Human Immunodeficiency Virus/Hepatitis C Virus–Coinfected Patients

2018

Vitamin D and Genetic Susceptibility to Multiple Sclerosis.

2019

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS), resulting from the interaction among genetic, epigenetic, and environmental factors. Vitamin D is a secosteroid, and its circulating levels are influenced by environment and genetics. In the last decades, research data on the association between MS and vitamin D status led to hypothesize a possible role for hypovitaminosis D as a risk factor for MS. Some gene variants encoding proteins involved in vitamin D metabolism, transport, and function, which are responsible for vitamin D status alterations, have been related to MS susceptibility. This review explores the current literature on the influence o…

Vitamin A Deficiency and the Lung.

2018

Vitamin A (all-trans-retinol) is a fat-soluble micronutrient which together with its natural derivatives and synthetic analogues constitutes the group of retinoids. They are involved in a wide range of physiological processes such as embryonic development, vision, immunity and cellular differentiation and proliferation. Retinoic acid (RA) is the main active form of vitamin A and multiple genes respond to RA signalling through transcriptional and non-transcriptional mechanisms. Vitamin A deficiency (VAD) is a remarkable public health problem. An adequate vitamin A intake is required in early lung development, alveolar formation, tissue maintenance and regeneration. In fact, chronic VAD has b…

Rescue of Hypovitaminosis A Induces Non-Amyloidogenic Amyloid Precursor Protein (APP) Processing.

2015

Retinoic acid, the bioactive metabolite of beta-carotene or vitamin A, plays a pleiotropic, multifunctional role in vertebrate development. Studies in rodents revealed that a diet deficient in vitamin A results in a complex neonatal syndrome (the VAD syndrome), manifested in many organs. In humans, the function of retinoic acid (RA) extends into adulthood, where it has important roles in fertility, vision, and suppression of neoplastic growth. In recent years, it has also been suggested that retinoic acid might potentially act as a therapeutically relevant drug in attenuating or even preventing neurodegenerative diseases such as Alzheimer's disease (AD). Here, we report that VAD leads to an…

Vitamin D receptor gene ApaI and FokI polymorphisms and its association with inflammation and oxidative stress in vitamin D sufficient Caucasian Span…

2021

Background Vitamin D has gone from being just one vitamin to being an important prohormone with multiple effects on different tissue types. The mechanism of action of the active form or calcitriol is mediated by the intracellular vitamin D receptor (VDR). The interaction of the VDR with calcitriol modulates the expression of target genes involved in cell proliferation and cytokine production. Several studies have explored the effects of vitamin D deficiency in inflammatory disorders. Furthermore, some mutations in the VDR can affect its functionality. The focus of this study was to explore associations between VDR single nucleotide polymorphisms (SNPs) and markers of inflammation and oxidat…

Vitamin D and Cardiovascular Health

2021

The principal source of vitamin D in humans is its biosynthesis in the skin through a chemical reaction dependent on sun exposure. In lesser amounts, the vitamin can be obtained from the diet, mostly from fatty fish, fish liver oil and mushrooms. Individuals with vitamin D deficiency, defined as a serum level of 25 hydroxyvitamin D < 20 ng/dl, should be supplemented. Vitamin D deficiency is a prevalent global problem caused mainly by low exposure to sunlight. The main role of 1,25 dihydroxyvitamin D is the maintenance of calcium and phosphorus homeostasis. However, vitamin D receptors are found in most human cells and tissues, indicating many extra-skeletal effects of the vitamin, particula…

Role of Vitamin A in Mammary Gland Development and Lactation

2019

Vitamin A (all-trans-retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription. Vitamin A deficiency is an important nutritional problem, particularly in the developing world. Retinol and carotenoids from diet during pregnancy and lactation influence their concentration in breast milk, which is important in the long term, not only for the offspring, but also for maternal health. …